Cardiovascular disease is commonly accepted as being one of the most serious health risks facing our society today. Diseased and obstructed coronary arteries can restrict the flow of blood and cause tissue ischemia and necrosis. After over two decades of investigation, the exact etiology of sclerotic cardiovascular disease is still in question, the treatment of narrowed coronary arteries is more defined. Surgical construction of coronary artery bypass grafts (CABG) is often the method of choice when there are several diseased segments in one or multiple arteries. Open heart surgery is, of course, very traumatic for patients. In many cases, less traumatic, alternative methods are available for treating cardiovascular disease percutaneously. These alternate treatment methods generally employ various types of percutaneous transluminal angioplasty (PTCA) balloons or excising devices (atherectomy) to remodel or debulk diseased vessel segments. A further alternative treatment method involves percutaneous, intraluminal installation of expandable, tubular stents or prostheses in sclerotic lesions.
A recurrent problem with the previous devices and PTCA procedures is their failure to maintain patency due to the growth of injured vascular tissue. This is known as “restenosis” and may be a result of the original injury to the vessel wall occurring during the angioplasty procedure. Pathologically restenosis represents a neointimal proliferative response characterized by smooth muscle cell hyperplasia that results in reblockage of the vessel lumen necessitating repeat PTCA procedures up to 35-50% of all cases. It has been generally accepted that certain therapeutic agents or medicaments may be capable of selectively inhibiting the growth of these hyperproliferating smooth muscle cells and thereby reduce the rate of restenosis after the primary interventional procedure.
Heretofore, various devices have been disclosed which may be used to deliver a therapeutic agent or medicament to a blood vessel while undergoing angioplasty. Balloon angioplasty catheters have been used to place and deliver various therapeutic agents or medicaments within human vessels. For example, in U.S. Pat. Nos. 5,112,305, 5,746,716, 5,681,281, 5,873,852, 5,713,863 and 6,102,904 disclose and claim a balloon catheter system with various injector plates mounted on the balloon for delivering a drug into an arterial segment.
Alternatively a standard angioplasty balloon may be coated with a substrate or polymeric material which either incorporates, or is then used to bond, certain medicaments or theraputic agents. These agents are then delivered to the desired therapeutic site by inflation of the balloon and diffusion of the medicament or therapeutic agent into the vessel wall. Only limited quantities of therapeutic agents can be delivered because of “wash-out” of the drug into the circulation during balloon placement and due to the limited time the inflated balloon can be left in place due to ischemia caused by the balloon.
In addition, previously disclosed methods of delivering drug to a site of treatment are described which utilize iontophoretic or electrophoretic means as disclosed in U.S. Pat. No. 5,499,971. Using these iontophoretic or electrophoretic means passive diffusion of the drug or medicament is enhanced by placing the medicament or therapeutic agent in close proximity to the site of treatment and then using electrical energy to augment delivery of the drug into the tissues or cells. These methods generally place the drug inside a balloon mounted distally on a catheter whereby the balloon is composed of a semi-porous material through which the drug can diffuse.
Additional devices have been disclosed which attempt to improve the depth of penetration into tissue by pressure driving a solution of the drug into the vessel wall through small orifices in the balloon material. There is, however, some evidence that high pressure “jetting” of a drug solution out of small pores close to the vessel lumen can in fact cause vessel wall injury. The development of double skinned, microporous (or weeping) balloons obviated this “jetting” effect to some extent, but diffusion of the drug into the vessel wall is still slow, and much of the drug can be lost through subsequent “washout effects”. This method leads to limited amounts of drugs or therapeutic agents delivered to the tissues or cells. Furthermore, in all of these methods the balloon must be expanded and thereby restricts blood flow to the distal arterial segments while the balloon is in the expanded configuration thus limiting the time the drug delivering balloon can be clinically utilized.
There are also several disadvantages using either a stent or balloon catheter to deliver a therapeutic agent or medicament to a vascular segment. Regarding the therapeutic agent eluting stents, once the stent is deployed, there is no means outside of invasive surgical excision, to remove the eluting stent from the vascular segment. Therefore, stents or implanted prostheses with therapeutic agent eluting properties must be precisely calibrated to deliver an exact quantity of the therapeutic agent or medicament to the vascular segment upon stent deployment. Balloon catheters employed to deliver a therapeutic agent or medicament to a vascular segment have limitations including potential balloon rupture and ischemia due to balloon inflation limiting distal blood flow to the artery. This leads to tissue ischemia and potential necrosis. Even “perfusion” type angioplasty balloons used to delivery a therapeutic agent or medicament to the affected artery provide far less than physiological blood flow during balloon inflation and dwell times are limited by ischemia and tissue necrosis.
Additional devices have been disclosed which utilize catheter based multiple injecton ports to inject the drug directly into the vessel walls. Disadvantages of this system include potential injury to vessel walls, non-uniform drug delivery and the requirement that the drug must be carried either in the solubilized form or in fine suspensions which is a particular problem for drugs that are not water-soluble).
Recent studies have demonstrated the effectiveness of a number of agents (e.g., paclitaxel, rapamycin, Actinomycin D) on the prevention of unwanted cellular proliferation. These agents have proven efficacy in the treatment of cancer transplant rejection and restenosis following angioplasty. A major advantage of these agents is their high lipid solubility that causes tissue levels of these agents to remain high for an extended period of time since they cannot be rapidly cleared. However, the delivery of these lipophillic medicaments generally present formulation and transport challenges in aqueous media. Furthermore, they are less likely to permeate across hydrophilic boundries and cell membranes into tissue.
Recently various genetic agents such as DNA, RNA, and antisense oligonucleotides have shown promises in treating certain disease states. In-vivo delivery of these genetic agents is currently carried out with viral vectors or viral compounds may oftern lead to very undesirable side effects.
Thus, it can be seen that there is a need for a new and improved apparatus and method to selectively deliver a therapeutic agent or medicament to an arterial segment or other selected sites in a body, and which overcomes these disadvantages.
In general, it is an object of this present invention to provide a catheter coated with a hydrogel copolymer encapsulating one or more medicaments that is capable of delivering, by an active means, the medicament(s) to the vessel segment or obstruction.
In general, it is an object of this present invention to provide a catheter system whereby the catheter can be charged with an electrical energy and the electrical energy will facilitate the release of medicaments present in an encapsulated state in a hydrogel or polymer present on a portion of the catheter and augmenting transport of the medicaments into surrounding tissues.
In general, it is an object of this present invention to provide a method whereby the medicament is released from the hydrogel and transported into the surrounding tissues through the electrophoretic, iontophoretic or electro-osmotic processes, or the combination of the above processes. The delivery of the medicaments is can be without a charged carrier or with one or more charged carriers. The charged carriers can be charged surfactants, polyelectrolytes, liposomes or other charged entities including, but no exclusively, small ions.
Another object of the invention is to provide a method to deliver high concentrations of agents that are poorly soluble or insoluble in aqueous media to selected sites in the body including arteries, veins or other tubular structures, prosthetic devices such as grafts, and tissues such as, but not limited to, brain, myocardium, colon, liver, breast and lung.
Another object of the invention is to provide an apparatus and a method to deliver a wide range of medicaments with different degrees of solubility, molecular sizes and chemical structures These medicaments can be charged or neutral. The medicaments can include, but not exclusively, genetic agents
Another object of the invention is to provide an apparatus and a method that can control the active release or diffusion of a medicament or therapeutic agent to minimize potential systemic effects and promote and maximize the delivery of the medicament or therapeutic agent into the surrounding tissue
Another object of the invention is to provide an apparatus and a method to promote and maximize the penetration of a medicament or therapeutic agent into the surrounding tissues uniformly throughout the diseased area and to facilitate the binding to the tissue and thus promote a therapeutic effect.
Another object of the invention is to provide a apparatus and method that can promote the active release or diffusion of a medicament or therapeutic agent while simultaneously dilating an obstruction within a blood vessel or organ.
Another object of the invention is to provide a apparatus and method that can promote the active release or diffusion of a medicament or therapeutic agent while simultaneously allowing perfusion of blood or liquid to occur through the apparatus delivering the medicament or therapeutic agent.